Platelet physiology II - stages of maturation

What is the origin of platelets?

megakaryocytes

Where do megakaryocytes originate?

the bone marrow

What is thrombopoesis?

platelet production

What molecule regulates thrombopoesis?

TPO, or thrombopoetin

Through the maturation stages of megakaryocytes, describe the general characteristics observed (size, cytoplasm stain, granule presence, nucleus:cytoplasm ratio, and nuclear lobing).

Size: goes from small to large

cytoplasm stain: goes from basophilic (deep blue) to acidophilic (pink)

granule presence: no granules to more

nucleus:cytoplasm ratio: high to low

• aka nucleus shrinks and cytoplasm grows

nuclear lobing: no lobing to multilobed

What is the normal lifespan of a platelet?

8-10 days

What is the reference range of platelets in peripheral blood?

150-450 × 10³/uL

Describe the megakaryocyte stage of maturation.

• derive from a unipotential stem cell

• nucleus is round, no lobes

• basophilic cytoplasm

• very small

• many copies of DNA due to endomitosis

Describe the promegakaryocyte stage of maturation.

• less DNA replication occurring

• deeper purple nucleus

• cytoplasm begins to lighten

• a few granules present

Describe the granular megakaryocyte stage of maturation.

• cytoplasm still lightening

• cytoplasm grows more, nucleus size decreases

• pinker granules

• no visible nucleoli

• multilobed, condensed nucleus

Describe the mature megakaryocyte stage of maturation.

• multilobed nucleus

• platelet fields (demarcation zones) form from granules

• acidophilic cytoplasm

• eventual breakage of the megakaryocyte releasing platelets and the nucleus

How are platelets removed?

macrophage consumption

How are platelets consumed?

through primary hemostasis, or storage in the spleen

What is the normal distribution of platelets?

2/3 in circulation, 1/3 in spleen

What is a splenectomy? How does it impact platelet distribution?

when the spleen is removed

Platelet distribution is increased in circulation

What is splenomegaly? How does it impact platelet distribution?

When the spleen is overactive/dysfunctional

Platelet distribution decreases in circulation (spleen basically hogs the platelets)

What is thrombopoetin (TPO)?

a regulator of megakaryocyte maturation and platelet development

• regulates endomitosis

• regulates production of megakaryocytes from unipotential cells

• increases platelet numbers and volumes in circulation

If a person receives a platelet transfusion, how does that impact their platelet count and free TPO availability?

Platelet count increases, therefore more platelet receptors for TPO, and thus decreased free TPO

If a person endures trauma (loss of platelets), how does that impact their platelet count and free TPO availability?

Platelet count decreases, therefore there are less platelet receptors for TPO, and thus increased free TPO

What are conditions that lead to increased bleeding time?

von Willebrands disease (platelet aggregation with vWF forming multimers)

platelet abnormalities

aspirin medication (TXA2 inhibitor)

thrombocytopenia (low platelet count)

Describe the platelet aggregation test.

Platelet rich plasma is stirred, and inoculated with collagen or epinephrine to induce aggregation

As the platelet changes shape for aggregation, the light transmittance changes

What is the relationship between platelet aggregation and light transmittance?

Initially, when a platelet agonist is added, light transmittance decreases as platelets change shape.

Then, as the platelets reach 100% aggregation, light transmittance increases as the aggregate falls to the bottom of the tube.

For the platelet function assay, if a sample of blood has a normal closure time after only COL/EPI, what is the interpretation?

Normal platelet fx

For the platelet function assay, if a sample of blood has a prolonged closure time with COL/EPI and a normal closure time with COL/ADP, what is the interpretation?

Normal closure time, likely thrown off by an aspirin medication

For the platelet function assay, if a sample of blood has a prolonged closure time with COL/EPI and a prolonged closure time with COL/ADP, what is the interpretation?

Potential disease such as von Willebrand’s disease, thrombocytopenia (low platelet count), or a platelet defect